Jack Allen

Jack Allen asked for clarification on the third-quarter R&D expenses, specifically regarding pre-launch manufacturing spend, and the R&D runway. He also inquired about the commercial opportunity for osteogenesis imperfecta compared to XLH, including pre-launch efforts and market analysis.

Answer

Howard Horn, Chief Financial Officer, clarified that the increase in Q3 R&D expenses to $216 million was due to investments in pre-launch inventory and preparations for upcoming launches. Emil Kakkis, CEO and President, stated that the OI patient population is estimated to be 50%-100% larger than XLH, with similar pricing expectations, making the OI opportunity larger than the XLH program.

Jack Allen inquired about the third-quarter R&D expenses, specifically the pre-launch manufacturing spend, and asked for insights into the future R&D runway. He also asked for a comparison of the commercial opportunity for osteogenesis imperfecta (OI) relative to XLH, based on pre-launch market analysis.

Answer

Howard Horn, Chief Financial Officer, clarified that the $216 million R&D expense in Q3 was higher than the trend due to strategic investments in pre-launch inventory for upcoming product launches. Emil Kakkis, CEO and President, stated that the OI patient population is estimated to be 50% to 100% larger than XLH, and with expected pricing similar to Crysvita, the OI opportunity is projected to be larger than the XLH program.

Jack Allen from Baird inquired about the standard deviation observed in the blinded ORBIT trial data, confidence in the statistical analysis plan (SAP), and whether there were any plans to present updated data from the Phase II cetrusumab cohort.

Answer

Emil Kakkis, Founder, President & CEO, did not provide the standard deviation but acknowledged significant variation. He expressed confidence in the negative binomial model used in the SAP, noting it's the best method for fracture data and allows for co-variables to manage variation. He also stated there are no specific plans yet to present updated Phase II data.

Jack Allen asked for clarification on how many patients in the setrusumab trial had 12 months of data at the first interim readout and inquired about any disclosures regarding the drug's impact on bone pain.

Answer

CEO Emil Kakkis explained that due to a 'hockey stick' enrollment pattern, the vast majority of patients had less than one year of data at the first interim. CMO Eric Crombez added that while they are formally tracking pain, they have heard significant anecdotal reports of pain improvement from the Phase II study. Kakkis noted that, similar to Crysvita, patients feeling better and becoming more active is a powerful, tangible benefit that drives enthusiasm for the therapy.

Jack Allen requested more context on what triggers the setrusumab interim analyses, asking if the timing is now fixed or still dependent on accruing fracture events.

Answer

CEO Emil Kakkis clarified that the interim analyses are now set on a fixed timeline (year-end/early 2025 and mid-2025). He explained this was an operational choice to simplify planning, as the original event-based trigger was challenging. The timeline was set by estimating when fracture event milestones would be hit, and they are confident the actual fracture rate will be sufficient by those dates.

Jack Allen of Baird asked about the confidence in the durability of remissions based on MRD conversion, and what patient numbers might be expected in the ALLO-329 autoimmune disease data readout next year.

Answer

CMO Dr. Zachary Roberts expressed confidence that MRD conversion is a strong correlate for long-term disease control based on growing data in the field. Regarding ALLO-329, he stated that while specific numbers were not being provided, the company expects to share a 'meaningful amount of data' in the first half of 2026.

Representing Jack Allen, Nick asked about the potential impact of the new CBER Director on the broader autoimmune opportunity for cell therapies.

Answer

CEO David Chang expressed confidence, emphasizing that the FDA is an institution that follows established guidance. He differentiated autoimmune trials from oncology, noting their endpoints are based on symptom improvement, not overall survival. He does not foresee new hurdles for advancing CAR T in autoimmune diseases, provided the safety and efficacy data are strong.

Jack Allen from Baird requested details on the ALPHA3 futility analysis, asking if it's a comparison against the control arm or a hurdle rate, and which metrics like MRD conversion or response rates would be used.

Answer

Dr. David Chang, President and CEO, clarified that it is a standard futility analysis assessing the totality of data. The key efficacy metric will be the MRD conversion rate, with the expectation of a significantly higher rate in the treatment arms compared to the observation arm. Safety will also be assessed for balance across arms.

Jack Allen asked for an update on the ALPHA2 study in CLL, including its status and go-forward path. He also inquired about the durability bar for the ALLO-316 program in RCC compared to the existing standard of care.

Answer

Dr. David Chang, President and CEO, confirmed the CLL study is ongoing but is subject to a pipeline prioritization, with ALPHA3 and ALLO-329 being the top priorities; an update is planned for next year. Dr. Zachary Roberts, EVP of R&D and CMO, explained that for ALLO-316, the durability bar is quite low, as third-line RCC therapies offer modest PFS of only a few months with continuous treatment. He noted the RMAT designation and high investigator enthusiasm support the program's potential.

Jack Allen from Baird sought clarification on the current status of regulatory interactions, specifically regarding the IND amendment with the FDA and any ongoing discussions with European authorities.

Answer

CEO Sean Nolan detailed the regulatory progress, noting that Health Canada issued a 'no objection letter,' clearing the trial to proceed. For the FDA, he confirmed receipt of correspondence indicating no clinical hold concerns, allowing them to proceed at their discretion. He characterized ongoing FDA dialogue as constructive and focused on refining program details for success. Additionally, he mentioned a scientific advice meeting with European regulators is scheduled for the early fall.

Jack Allen from Baird asked for color on FDA interactions following recent leadership changes at the agency and inquired about the consistency of the review team.

Answer

CEO Sean Nolan assured that the core FDA review team has remained consistent and that interactions after Dr. Peter Marks' departure were unaffected, with meetings proceeding on schedule. President and Head of R&D Sukumar Nagendran added that the team reviewing the Rett program has been stable, expressing confidence in the agency's data-driven approach under new leadership.

Jack Allen asked for details on the clinical trial sites where the high-dose patients were treated, seeking to understand the expansion of the trial's footprint and physician experience with TSHA-102.

Answer

CEO Sean Nolan clarified that Taysha has five active dosing sites for the REVEAL trials. He confirmed that patients in the high-dose cohort have been treated at a minimum of two different sites, and across the entire program (low and high doses), at least three distinct sites have now administered the therapy.

Jack Allen inquired about the baseline characteristics of the enrolled high-dose patients and the company's expectations for how the low-dose data will evolve over time.

Answer

President and Head of R&D, Sukumar Nagendran, noted that high-dose patients will have baseline CGIS scores in the 4-6 range per protocol and exhibit common Rett syndrome features. CEO Sean Nolan added that the expectation for low-dose patients is to see continued progress, similar to the first patient who showed ongoing improvements in motor function and communication. He expressed hope for potentially better progress in the younger pediatric patients over time.

Jack Allen from Baird requested additional details on the powering assumptions for the TEBI-AM trial, particularly the expected overall survival in the control arm, and asked if data for PWELL and PRAME half-life extension could also be expected next year.

Answer

David Berman, EVP of R&D, stated the trial is modeled on a historical one-year survival of 55% for the control arm. He confirmed that dose escalation for both PWELL and the PRAME half-life extension (HLE) should complete in the next 12 months, making it possible that HLE data could also be shared next year.

On behalf of Jack Allen from Baird, an analyst asked about the pivotal PRISM-MEL study for brenetafusp, seeking details on the metrics the IDMC will use for the dose selection decision, whether the company will receive the interim data, and if a futility analysis is included.

Answer

CEO Bahija Jallal confirmed that the interim data will not be released publicly to maintain trial integrity. David Berman, Head of R&D, added that there is no futility analysis planned. The IDMC will use both efficacy and safety data to select a dose, looking for large differences between the two active doses and using modeling for support if needed.

Jack Allen of Baird asked about the timeline for seeing clinical data from earlier-stage pipeline assets, specifically the PIWIL program, the Half-Life Extended PRAME, and the PRAME-A24 program.

Answer

Mohammed Dar, an executive, stated that for the PIWIL program, they aim to enroll the first patient by year-end. The Half-Life Extended PRAME has been submitted for regulatory feedback, and the A24 version is on track for submission by year-end. He noted it's too early to guide on data timelines. David Berman, Head of R&D, added that learnings from existing programs are being applied to accelerate these Phase I trials.

Jack Allen of Baird asked about the timeline for seeing clinical data from the earlier-stage pipeline assets, including the PIWIL, Half-Life Extended PRAME, and PRAME-A24 programs.

Answer

Mohammed Dar, an executive, provided updates on program progress, including PIWIL site activation and HLE PRAME submission, but stated it was too early to guide on data timelines for these first-in-human trials. David Berman, Head of R&D, added that learnings from the current platform are being applied to accelerate these new trials.

Jack Allen from Baird questioned the bar for success and durability expectations for UCART22 in relapsed/refractory ALL, inquired about the company's view on Allogene's move away from CD52 lymphodepletion, and asked about infection risk mitigation strategies.

Answer

Chief Medical Officer Dr. Adrian Kilcoyne stated that durability is critical and regulators have agreed on the use of short-term surrogate endpoints for the primary analysis, with more details to come at the R&D Day. Regarding Allogene, both Dr. Kilcoyne and CFO Arthur Stril emphasized that Cellectis's situation is different due to product positioning, lower dosing, and the use of actual alemtuzumab from Sanofi, making comparisons difficult. Dr. Kilcoyne also noted that mandatory prophylaxis is already built into trials to mitigate infection risk.

Jack Allen asked about Cellectis's internal success criteria for the UCART22 readout, the clinical timeline for AstraZeneca programs, the novelty of their targets, and any updates on the Servier arbitration. He later followed up on the Servier litigation, the implications of CARGO's discontinued CD22 asset, and the durability data from Allogene's cema-cel program.

Answer

CEO Dr. André Choulika expressed confidence in the UCART22 data for the heavily pretreated patient population. CBO Arthur Stril noted the AstraZeneca collaboration is progressing well across multiple therapeutic areas with potential data this year, but declined to comment on the ongoing Servier arbitration. Regarding CARGO's discontinuation, Stril and CMO Dr. Adrian Kilcoyne viewed it as confirmation of the market need for non-CD19 therapies and stated the toxicity issues are not inherent to the CD22 target. Stril also highlighted Allogene's cema-cel data as very encouraging for the durability of allogeneic platforms.

Asked about the UCART20x22 program, questioning the need for dose escalation given the strong initial results, and requested more detail on the data cut-off and expected follow-up for the ASH presentation.

Answer

Despite the strong initial results and good safety profile, the company will proceed with dose escalation for UCART20x22. The ASH poster presentation will focus on providing further follow-up on the initial three patients.

Jack Allen from Baird asked about the potential structure of future manufacturing partnerships and sought a timeline for data from the OPC1 DOSED study, as well as its potential interplay with other device technologies.

Answer

CEO Brian Culley explained that partnership goals involve milestone payments and asset ownership, not becoming a contract manufacturer (CDMO). He stated that for the OPC1 study, data on the delivery device's safety (a 30-day endpoint) would be available on a rolling basis, while functional data would lag by 6-12 months. He also noted OPC1 could be complementary to other technologies.

Jack Allen of Robert W. Baird & Co. asked about Lineage's strategy to protect its market leadership in RPE cell replacements amid a growing competitive landscape. He also inquired about the timeline for the updated 3-year OpRegen data and how positive RPE results serve as a proof of concept for the broader Lineage platform, including OPC1.

Answer

CEO Brian Culley emphasized that Lineage's competitive advantage is a "triumvirate" of its advanced manufacturing, Genentech's development expertise, and Roche's commercialization leadership. He stated that while Genentech controls the timing of the 3-year data release, the positive effects have been confirmed to persist. Culley positioned non-oncology cell therapy as a major growth area, suggesting that successes in RPE transplants validate the cell replacement approach for other conditions like spinal cord injury.

Jack Allen of Robert W. Baird & Co. inquired about the data used to secure the RMAT designation for OpRegen, the potential timing for 3-year follow-up data, Roche's next steps for the program, and whether natural examples of hearing regeneration exist.

Answer

CEO Brian Culley stated he was unable to comment on the specifics of the RMAT submission or future data release timelines, as those are controlled by their partner, Roche/Genentech. He speculated that a large Phase IIb study, similar to Iveric's strategy, could serve as a registrational trial for OpRegen. He also confirmed that natural hearing regeneration occurs in species like birds, which serves as a scientific precedent for the ANP1 program's approach.

Jack Allen of Robert W. Baird & Co. questioned the timing for accessing CIRM grant capital after IND clearance and asked about the OpRegen Phase I/II patient follow-up. Specifically, he asked about the rationale for extending the follow-up to a total of 10 years, rather than the 15 years sometimes guided by the FDA for cell therapies.

Answer

CFO Jill Howe explained that accessing CIRM funds would be a gradual process, not a lump sum, and may see delays due to a high volume of applications at CIRM. CEO Brian Culley addressed the follow-up extension, stating the original FDA-cleared protocol was for five years. He speculated that Genentech's interest in a 10-year total follow-up is to assess the long-term durability of the treatment, a key factor for its value proposition, rather than a new regulatory requirement for this specific program.

Jack Allen inquired about the expected timing for solidifying the NAIAD funding for the GvHD study, any backup funding plans, and the company's current cash runway.

Answer

President and CEO Dr. Jennifer Buell stated that the NAIAD funding timeline is fluid but expressed optimism, noting the trial is submitted and ready to proceed once funding is cleared. She mentioned backup strategies include partner interest and targeted financing. Dr. Buell also confirmed that the company's current cash position provides a runway through the end of 2025.

Jack Allen asked for additional details on key external tau program readouts to watch at the upcoming AD/PD conference and inquired about potential milestones from partnered programs, specifically asking if they are included in the current cash runway guidance.

Answer

CEO Dr. Al Sandrock highlighted expectations for bepranemab PK/PD data and subgroup analysis at AD/PD, along with potential updates from Eisai and Biogen. CFO Dr. Nathan Jorgensen clarified that the potential $8.2 billion in milestones, including $2.9 billion in developmental milestones, are not factored into the mid-2027 cash runway guidance and represent pure upside.

Jack Allen inquired about the progress of Voyager's blood-brain barrier (BBB) shuttle programs, potential timelines for clinical entry, and the company's interest in forming partnerships for these assets before generating clinical data.

Answer

CEO Dr. Alfred Sandrock and Chief Scientific Officer Dr. Todd Carter stated that while they are excited about leveraging their identified receptors to shuttle macromolecules across the BBB, the programs are still in the preclinical stage with no guided timeline for clinical entry. Dr. Carter noted that different receptors could offer unique pharmacokinetic and safety profiles. Dr. Sandrock affirmed that he is always open to discussing partnerships that could help accelerate these programs.

Jack Allen of Robert W. Baird & Co. inquired about the clinical trial cadence for the three gene therapy programs expected to file INDs in 2025 and how quickly biomarker impacts could be observed for the internal SOD1-ALS program.

Answer

CEO Dr. Al Sandrock stated that Voyager's wholly-owned SOD1 gene therapy program is targeting an IND filing around mid-2025, but the exact timing for the two partnered programs is determined by their partners. CMO Dr. Toby Ferguson explained that, based on data from Biogen's tofersen, CSF SOD1 reduction could be seen as early as 4-12 weeks and neurofilament changes around 8-16 weeks, though he cautioned that gene therapy timelines may differ from an ASO.

Jack Allen of Baird asked about Voyager's strategy for optimizing manufacturing before clinical trials, the expected cost-of-goods (COGS) benefits from more potent gene therapies, and the role of product shelf life in commercial applicability.

Answer

Executives Alfred Sandrock and Todd Carter detailed their process, which includes using HEK293 cells, assessing manufacturability during candidate selection, and transferring processes to CDMOs for scaling. They anticipate substantial COGS savings due to lower required doses from more potent capsids and expect continued cost reduction as manufacturing scale increases. They also confirmed that shelf life and stability are critical components of their process development.

Jack Allen inquired about the upcoming preclinical proof-of-concept (POC) for Editas' in vivo program, asking for specifics on the type of data, the animal model to be used, and the methods for assessing off-target editing.

Answer

Chief Scientific Officer Linda Burkly, after an introduction from CEO Gilmore O'Neill, confirmed the company is on track to establish in vivo preclinical POC by year-end. She stated the evaluation will assess biodistribution, editing efficiency, target modulation via biomarkers, and tolerability, with more details on the specific model and data forum to be announced later.

Inquired about the Reni-cel program, including the dosing status of the pivotal cohort, regulatory alignment on cohort size, and potential differentiation in the treatment process, such as apheresis cycles and manufacturing efficiency.

Answer

The adult cohort is fully enrolled, with many patients scheduled for dosing. The company has alignment with the FDA on the Phase I/II/III study design for a BLA filing. While specifics on apheresis cycles were not shared, the company has improved the process to reduce patient burden and smooth manufacturing, which will be beneficial for commercialization.

Asked about the patient experience with Reni-cel, including the number of apheresis cycles required, and the time to neutrophil engraftment compared to competing products.

Answer

The company has optimized the apheresis process and is pleased with the number of cycles required, noting it's an improvement. Regarding engraftment, all patients have successfully engrafted within 30 days, a result they are very happy with and continue to see consistently.

Inquired about the progress of studying LYFGENIA in younger patients and asked for details on the number of patients in the Bluebird support system and their potential pull-through rate.

Answer

A pediatric trial for LYFGENIA (HGB-210) is ongoing and expected to complete enrollment by Q4 2024. The company declined to comment on the number of patients in their support system or the pull-through rate, citing the early stage of the launch.

Inquired about the company's manufacturing capacity and its ability to handle a potential influx of patients, particularly in the second half of the year as LYFGENIA demand is expected to build.

Answer

The company stated that the supply chains for LYFGENIA and the other two products are separate. They have designed a larger capacity for LYFGENIA and have sufficient volume to meet initial launch expectations. They also have plans in place to expand capacity as demand increases over time.